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Starving for DENV vaccines: Nearly 50% of the world's population is considered at risk of infection with dengue virus (DENV), a mosquito-borne RNA virus that can potentially cause lethal disease. The efficacy of currently approved vaccines is poor in people who have not previously encountered DENV. Afroz et al. found that pretreatment of mice with the amino acid starvation mimetic halofuginone (HF) increased the adaptive immune response to a DENV vaccine. Known to activate the nutrient-sensing kinase GCN2, HF promoted phosphorylation of the translation initiation factor eIF2α in immune cells, increased germinal center formation, and increased neutralizing antibody responses. These data demonstrate how activation of this stress-induced kinase improves vaccination. Specific reduction in the intake of proteins or amino acids (AAs) offers enormous health benefits, including increased life span, protection against age-associated disorders, and improved metabolic fitness and immunity. Cells respond to conditions of AA starvation by activating the amino acid starvation response (AAR). Here, we showed that mimicking AAR with halofuginone (HF) enhanced the magnitude and affinity of neutralizing, antigen-specific antibody responses in mice immunized with dengue virus envelope domain III protein (DENVrEDIII), a potent vaccine candidate against DENV. HF enhanced the formation of germinal centers (GCs) and increased the production of the cytokine IL-10 in the secondary lymphoid organs of vaccinated mice. Furthermore, HF promoted the transcription of genes associated with memory B cell formation and maintenance and maturation of GCs in the draining lymph nodes of vaccinated mice. The increased abundance of IL-10 in HF-preconditioned mice correlated with enhanced GC responses and may promote the establishment of long-lived plasma cells that secrete antigen-specific, high-affinity antibodies. Thus, these data suggest that mimetics of AA starvation could provide an alternative strategy to augment the efficacy of vaccines against dengue and other infectious diseases. [ABSTRACT FROM AUTHOR]

The current review focuses on pathophysiology, animal models and molecular analysis of stroke and retinal ischemia, and the role of stem cells in recovery of these disease conditions. Research findings associated with ischemic stroke and retinal ischemia have been discussed, and efforts towards prevention and limiting the recurrence of ischemic diseases, as well as emerging treatment possibilities with endothelial progenitor cells (EPCs) in ischemic diseases, are presented. Although most neurological diseases are still not completely understood and reliable treatment is lacking, animal models provide a major step in validating novel therapies. Stem cell approaches constitute an emerging form of cell-based therapy to treat ischemic diseases since it is an attractive source for regenerative therapy in the ischemic diseases. In this review, we highlight the advantages and limitations of this approach with a focus on key observations from preclinical animal studies and clinical trials. Further research, especially on treatment with EPCs is warranted. J. Cell. Physiol. 227: 1269-1279, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Two images are presented which feature mouse retinal wholemounts showing vasculature in a retinal ischemia model.

Background: Genetic predisposition to ACL tears has received tremendous interest in the past few years with many SNPs of different genes being linked to ACL tear. Study Objectives: To examine if specific sequence variants in COL12A1 gene are associated with ACL tears in Indian population. Study design: Case-control study. Materials and methods: 50 patients with surgically diagnosed ACL tear and 52 healthy, agematched controls without any ligament/tendon injuries were genotyped for rs970547 and rs240736 SNPs using real time PCR method. Results: The AG and GG genotypes were significantly under-represented in study group patients in rs970547 region (p=0.0361). However, there was no significant difference in genotype/allele frequencies in the rs240736 region. Conclusions: The COL12A1 rs970547 SNP is associated with ACL tears in the Indian population. However, these results need to be validated further so that predisposed individuals can be screened in the future for counselling and intervention. Level of evidence: III [ABSTRACT FROM AUTHOR]